Oxidized LDL leads to podocyte injury through PTEN/SR-A pathway

Objective To evaluate the effect of oxidized LDL (Ox-LDL) on scavenger receptor A (SR-A) expression in mouse podocytes and to explore the possible mechanism. Methods The conditionally immortalized mouse podocyte cell line was cultured in vitro and exposed to Ox-LDL of different concentrations for 24 h, or 20 mg/L Ox-LDL for different hours. Cell cholesterol accumulation was examined. Real-time quantity PCR and Western blotting were used to analyze the expression level of PTEN, SR-A and nephrin. Podocytes were incubated with DiI labeled Ox-LDL for 4 h and immunofluorescence was used to analyze lipid uptaking. To further confirm the relationship between PTEN and SR-A, PTEN inhibitor bpv (hOpic) dipotassium bisperoxo (5-hydroxypyridine-2-carboxyl) oxovanadate (V) ], PTEN siRNA and PTEN adenovirus (adPTEN) were used to dual-directional regulate PTEN expression, so as to observe the change of SR-A, nephrin, cell cholesterol accumulation and lipid uptake. Results SR-A was expressed on mouse podocyte and mediated podocyte lipid uptake. Compared with control group, Ox-LDL increased cell cholesterol accumulation, and up-regulated SR-A expression along with inhibited expression of PTEN and nephrin (P＜0.05), which were correlate with dose and exposure time of Ox-LDL. Expression of PTEN significantly inhibits the expression level of SR-A and lipid uptake induced by Ox-LDL (P＜0.05), thereby decreasing cell cholesterol accumulation, but up-regulating nephrin level (P＜0.05). However, down-regulation of PTEN could cause opposite effect. Conclusion Ox-LDL up-regulates SR-A through decreasing the expression of PTEN, and contributes to podocyte injury.